Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
al
antimineralocorticoid
An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is ofte ...
of the
spirolactone
Spirolactones are a class of functional group in organic chemistry featuring a cyclic ester attached spiro to another ring system. The name is also used to refer to a class of synthetic steroids, called steroid-17α-spirolactones, 17α-spirol ...
group related to
spironolactone
Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood pressure ...
which is used as a
diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
in
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
, including in
Italy
Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
and
Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
.
It is also an important
active metabolite An active metabolite is an active form of a drug after it has been processed by the body.
Metabolites of drugs
An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...
of spironolactone, and partially accounts for its therapeutic effects.
Medical uses
Canrenone is mainly used as a
diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
.
Canrenone has been found to be effective in the treatment of
hirsutism
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
in women.
Heart failure
Two studies of canrenone in people with heart failure have shown a mortality benefit compared to placebo. In the evaluation which studied people with
chronic heart failure (CHF), people that were treated with canrenone displayed a lower number of deaths compared to the placebo group, indicating a death and morbidity benefit of the medication.
One study compared 166 treated with canrenone to 336 given conventional therapy lasting 10 years. Differences in systolic and diastolic blood pressure was observed between both patient groups where, patients treated with canrenone, showed a lower blood pressure compared to conventional therapy. Uric acid was lower in the group treated with canrenone; however, no differences were seen in potassium, sodium, and
brain natriuretic peptide
Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. Along with NT-proBNP, BNP is on ...
(BNP) levels. Left ventricular mass was also lower in the group treated with canrenone and a greater progression of NYHA class was observed in the control group compared to patients treated with canrenone.
Another study concluded that treatment with canrenone in patients with chronic heart failure improves diastolic function and further decreased BNP levels.
Pharmacology
Pharmacodynamics
Canrenone is reportedly more potent as an antimineralocorticoid relative to spironolactone, but is considerably less potent and effective as an
antiandrogen
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
.
Similarly to spironolactone, canrenone inhibits
steroidogenic
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
enzymes such as
11β-hydroxylase,
cholesterol side-chain cleavage enzyme
Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reactio ...
,
17α-hydroxylase,
17,20-lyase, and
21-hydroxylase, but once again, is comparatively less potent in doing so.
Pharmacokinetics
The
elimination half-life
Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of canrenone is about 16.5 hours.
As a metabolite
Canrenone is an
active
Active may refer to:
Music
* ''Active'' (album), a 1992 album by Casiopea
* Active Records, a record label
Ships
* ''Active'' (ship), several commercial ships by that name
* HMS ''Active'', the name of various ships of the British Royal ...
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
of spironolactone,
canrenoic acid
Canrenoic acid is a synthetic steroidal antimineralocorticoid which was never marketed.
See also
* Potassium canrenoate
* Canrenone
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antiminer ...
, and
potassium canrenoate
Potassium canrenoate ( INN, JAN) or canrenoate potassium (USAN) (brand names Venactone, Soldactone), also known as aldadiene kalium, the potassium salt of canrenoic acid, is an aldosterone antagonist of the spirolactone group. Like spironolact ...
, and is considered to be partially responsible for their effects.
It has been found to account for approximately 10 to 25% of the
potassium-sparing effect of spironolactone,
whereas another metabolite,
7α-thiomethylspironolactone
7α-Thiomethylspironolactone (7α-TMS; developmental code name SC-26519) is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and the major active metabolite of spironolactone. Other important metabolites of spironola ...
(7α-TMS), accounts for around 80% of the potassium-sparing effect of the drug.
History
Canrenone was described and characterized in 1959.
It was introduced for medical use, in the form of
potassium canrenoate
Potassium canrenoate ( INN, JAN) or canrenoate potassium (USAN) (brand names Venactone, Soldactone), also known as aldadiene kalium, the potassium salt of canrenoic acid, is an aldosterone antagonist of the spirolactone group. Like spironolact ...
(the
potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
of
canrenoic acid
Canrenoic acid is a synthetic steroidal antimineralocorticoid which was never marketed.
See also
* Potassium canrenoate
* Canrenone
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antiminer ...
), by 1968.
Society and culture
Generic names
''Canrenone'' is the and of the drug.
Brand names
Canrenone has been marketed under the brand names Contaren, Luvion, Phanurane, and Spiroletan, among others.
Availability
Canrenone appears to remain available only in
Italy
Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
, although potassium canrenoate remains marketed in various other countries as well.
See also
*
Canrenoic acid
Canrenoic acid is a synthetic steroidal antimineralocorticoid which was never marketed.
See also
* Potassium canrenoate
* Canrenone
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antiminer ...
*
Potassium canrenoate
Potassium canrenoate ( INN, JAN) or canrenoate potassium (USAN) (brand names Venactone, Soldactone), also known as aldadiene kalium, the potassium salt of canrenoic acid, is an aldosterone antagonist of the spirolactone group. Like spironolact ...
References
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Pharmacodynamics
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...
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{{Androgen receptor modulators
{{Mineralocorticoid receptor modulators
{{Progesterone receptor modulators
11β-Hydroxylase inhibitors
21-Hydroxylase inhibitors
Aldosterone synthase inhibitors
Antimineralocorticoids
Cholesterol side-chain cleavage enzyme inhibitors
CYP17A1 inhibitors
Diuretics
Human drug metabolites
Lactones
Pregnanes
Progestogens
Spiro compounds
Spirolactones
Spironolactone
Steroidal antiandrogens
World Anti-Doping Agency prohibited substances
Conjugated dienes
Enones